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IL-17E (IL-25) Enhances Innate Immune Responses during Skin Inflammation

Senra, Luisa
Mylonas, Alessio
Kavanagh, Ruairi D
Fallon, Padraic G
Conrad, Curdin
Borowczyk-Michalowska, Julia
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Published in Journal of investigative dermatology. 2019, vol. 139, no. 8, p. 1732-1742.e17
Abstract IL-17E (IL-25) is a member of the IL-17 cytokine family involved in the promotion of type 2 immune responses. Recently, IL-17E has been reported to be up-regulated in distinct skin inflammatory diseases such as psoriasis and atopic and contact dermatitis. We assessed the role played by IL-17E in skin inflammation. Here, we show that IL-17E induces skin inflammation in vivo, characterized by the expression of innate immune response genes and the recruitment of innate immune cells, particularly neutrophils. Genetic deletion or IL-17E neutralization ameliorated skin inflammation induced by imiquimod application or tape stripping, with reductions in neutrophil and macrophage infiltration as assessed by t-distributed stochastic neighbor embedding-guided multiparameter flow cytometry analysis, in mice. In humans, IL-17E promotes the recruitment of neutrophils via activation of macrophages in a p38-dependent mechanism. In addition, IL-17E is up-regulated in neutrophil-rich inflammatory skin diseases, such as pyoderma gangrenosum and acute generalized exanthematous pustulosis. Our data show a role for IL-17E in skin inflammation that is unrelated to the development of type 2 immune reactions. We propose that IL-17E is an important common denominator of chronic skin inflammation, promoting innate immune cell recruitment and activation.
Keywords Acute Generalized Exanthematous Pustulosis/immunology/pathologyAdjuvants, Immunologic/administration & dosageAnimalsDermatitis/immunology/pathologyDisease Models, AnimalFemaleHumansImiquimod/administration & dosageImmunity, InnateInterleukin-17/immunology/metabolismInterleukins/genetics/immunology/metabolismMacrophages/immunology/metabolismMiceMice, KnockoutNeutrophils/immunology/metabolismPyoderma Gangrenosum/immunology/pathologySkin/cytology/immunology/pathologyUp-Regulationp38 Mitogen-Activated Protein Kinases/metabolism
PMID: 30738055
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Research group Mécanismes des pathologies de l'inflammation cutanée (919)
Swiss National Science Foundation: 310030_152680
Swiss National Science Foundation: 310030_175470
(ISO format)
SENRA, Luisa et al. IL-17E (IL-25) Enhances Innate Immune Responses during Skin Inflammation. In: Journal of Investigative Dermatology, 2019, vol. 139, n° 8, p. 1732-1742.e17. doi: 10.1016/j.jid.2019.01.021 https://archive-ouverte.unige.ch/unige:137814

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Deposited on : 2020-06-24

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